Biochemistry of Vitamin K
GIT | 1 Lecture | Dr. Usman Ghani
Overview Types and chemistry of vitamin K Sources and daily requirements Functions: Synthesis of -carboxyglutamate in:
Prothrombin and blood clotting factors Osteocalcin Interaction of prothrombin with platelets
Deficiency and disorders Clinical manifestations
Types and Chemistry
Occurs in several forms:
Vitamin K1 (Phylloquinone)
Vitamin K2 (Menaquinone)
Vitamin K3 (Menadione) – synthetic form
Types and Chemistry
Vitamin K1 (Phylloquinone)
Vitamin K2 (Menaquinone)
Vitamin K3 (Menadione)
Sources of Vitamin K
Phylloquinone: Green leafy vegetables Menaquinone: Intestinal bacteria
Intestinal bacterial synthesis meets the daily requirement of vitamin K even without dietary supplement
Menadione: synthetic form
RDA for Vitamin K (g/day)
Infant (0-1 year): 2-2.5 Children (1-8): 30-55 Men (19+): 120 Women (19+): 90 Pregnancy / lactation: 90 / 90 UL: Not established
Functions ofVitamin K
Coenzyme for the synthesis of prothrombin and blood clotting factors in the liver Prothrombin and clotting factors are
protein in nature Synthesis of prothrombin, clotting
factors VII, IX, X require carboxylation of their glutamic acid (Glu) residue
Active form
Warfarin
Functions ofVitamin K
Mature prothrombin and clotting factors contain -carboxyglutamate (Gla) after carboxylation reaction
Vitamin K is essential for the carboxylase enzyme involved
Dihydroquinone form of vitamin K is essential for this reaction
Active form
Warfarin
Functions ofVitamin K
Anticoagulant drugs: warfarin and dicoumarol Structural analogs of vitamin K
They inhibit the activation of vitamin K to hydorquinone form
Hence prothrombin and clotting factors are not carboxylated
Blood coagulation time increases upon injury
Prothrombin – platelet interaction
Functions of Vitamin K
Prothrombin – platelet interaction Carboxylated prothrombin contains two
carboxylate groups (COO–) These groups bind to Ca2+ forming prothrombin-
calcium complex The complex then binds to phosholipids on the
surface of platelets (important for blood clotting) Converting prothrombin to thrombin and
initiating clot formation
Functions ofVitamin K
Synthesis of -carboxyglutamate in osteocalcin Osteocalcin is a bone protein May have a role in bone formation and
mineralization -carboxyglutamate is required for osteocalcin
binding to hydroxyapatite (a mineral) in the bone
The function of bone osteocalcin is unclear
Deficiency of Vitamin K
Deficiencies are rare: it is synthesized by the intestinal bacteria
Hypoprothrombinemia: increased blood coagulation time
May affect bone growth and mineralization
Malabsorption of lipids leads to vitamin K deficiency
Deficiency of Vitamin K
Prolonged antibiotic therapy Gastrointestinal infections with diarrhea
Both of the above destroy the bacterial flora leading to vitamin K deficiency
Deficiency most common in newborn infants Newborns lack intestinal flora Human milk cannot provide enough vitamin K Supplements are given by injection
Clinical Manifestations of the Deficiency Hemorrhagic disease of the newborn
Bruising tendency, ecchymotic patches (bleeding underneath the skin)
Mucus membrane hemorrhage
Post-traumatic bleeding / internal bleeding
Prolonged prothrombin time